Nighttime Breathing Disorder Effects Are Independent of Obesity

Action Points

Explain to interested patients that sleep apnea and other sleep disordered breathing problems are often seen in conjunction with obesity.

Note that three observational studies could not determine causal relationships.

BALTIMORE, Jan. 23 -- Sleep disordered breathing and obesity often go hand in hand, but their links to negative health outcomes and lifestyles are independent, three separate studies revealed.

Obesity and sleep disordered breathing exert separate effects on the liver and insulin resistance that make the conditions greater cause for concern when they occur together than alone, researchers from Johns Hopkins reported in two studies in the Feb. 1 issue of the American Journal of Respiratory and Critical Care Medicine.

Another study in the same issue found that a sedentary lifestyle is a risk factor for obstructive sleep apnea irrespective of weight.

The studies reflect the recent evolution in sleep research toward a more nuanced view of the effects of nighttime breathing disorders.

They found that the more severe the sleep disordered breathing, the worse the insulin resistance. Compared with patients who breathed normally during sleep, insulin sensitivity fell by 26.7% as the apnea-hypopnea index rose from five to 14.9. It fell by 36.5% as the index rose from 15 to 29.9, and by 43.7% at 30 or more events per hour (P<0.007 for trend).

Insulin sensitivity and pancreatic beta-cell function measured with the disposition index also fell with increasing severity of sleep disordered breathing reflected in the degree of oxyhemoglobin desaturation.

Every 1% increase in average oxygen desaturation was associated with a 5.7% decrease in average disposition index (P=0.065).

Glucose effectiveness also fell as the frequency of respiratory event-related arousals rose, even after accounting for oxygen saturation.

"Collectively, these defects may increase the risk of glucose intolerance and type 2 diabetes mellitus in sleep disordered breathing," the researchers wrote.

In a second study, researchers led by Vsevolod Y. Polotsky, M.D., Ph.D., of Johns Hopkins, again linked sleep disordered breathing to insulin resistance in the obese and also showed an independent effect on liver function.

They performed sleep studies on 90 consecutive severely obese patients (BMI over 35 kg/m2) who had routine liver biopsies during bariatric surgery.

Chronic intermittent hypoxia also had an independent effect on C-reactive protein and nonalcoholic fatty liver disease in severely obese patients.

Histopathology suggested that severe nocturnal oxygen desaturation elevated hepatic inflammation, hepatocyte ballooning, and liver fibrosis. But because BMI was similar across patient groups, the researchers said obstructive sleep apnea appeared to have an independent detrimental effect on the liver.

They hypothesized that severe obesity "acts as 'the first hit' in the progression of nonalcoholic fatty liver disease inducing hepatic steatosis, whereas the presence of chronic intermittent hypoxia of obstructive sleep apnea acts as the 'second hit,' inducing progression of hepatic steatosis to nonalcoholic steatohepatitis."

A third study found a link with a sedentary lifestyle as well.

Earlier studies by T. Douglas Bradley, M.D., of Toronto General Hospital, and colleagues suggested that fluid accumulation in the legs from long periods of sitting during the day increases the collapsibility of upper airways when it redistributes at night.

To see whether this had an impact on sleep disordered breathing, they analyzed sleep studies of 23 nonobese healthy men referred for suspected obstructive sleep apnea.

As expected, decreases in leg fluid volume from the beginning to the end of the night correlated strongly with increases in neck circumference (P<0.001) and how long the men spent sitting the day before (P=0.003).

Notably, these changes in fluid volumes were strongly linked to the apnea-hypopnea index (P<0.001).

In the multivariate analysis, overnight changes in leg fluid volume and neck circumference -- not body mass index -- were the only significant factors for the apnea-hypopnea index and together explained 68% of its variability.

These results suggest that a sedentary lifestyle "may play a previously unrecognized role in the pathogenesis of obstructive sleep apnea in nonobese men that is independent of body weight," Dr. Bradley's group said.

All three research groups noted that their observational studies could not determine causality.

Dr. Punjabi's study was supported by grants from the National Center for Research Resources, NIH Roadmap for Medical Research, and National Heart, Lung, and Blood Institute.

Dr. Punjabi reported conflicts of interest for Respironics and Resmed.

Dr. Polotsky's study was supported by NHLBI grants and by the Johns Hopkins Bayview General Clinical Research Center.

Her group reported no conflicts of interest.

Dr. Bradley's study was supported by a grant from the Canadian Institutes of Health Research.

A co-author reported conflicts of interest for Fuji-Respironics. Co-authors reported support by fellowships from the University of Brescia, the Toronto Rehabilitation Institute, Fuji Respironics, Siriraj Hospital in Bangkok, the Toronto Rehabilitation Institute, Chang Gung Memorial Hospital, Kaohsiung Medical Center, and the Chang Gung University College of Medicine.

Reviewed by Zalman S. Agus, MD Emeritus Professor University of Pennsylvania School of Medicine

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.